Cell migration and the anatomic control of thymocyte precursor differentiation

The thymus performs several essential functions during the steady-state pro duction of T lymphocytes in adults, including expansion of the precursor po ol, differentiation into multiple lineages and screening for TCRs with rest ricted specificities. Other than those functions attributed to the TCR, mos t of the factors that control these processes remain undefined. One potenti al mechanism for such control may, be related to the movement of precursor cells between distinct anatomical compartments in the thymus. Histological studies show that the majority of CD4(-) CD8(-) cells are found in the subc apsular region. However, vascular tissues that support the migration of pre cursor cells into the thymus (post-capillary venules) are located deep in t he tissue, near the cortico-medullary junction. This implies that blood-bor ne cells entering the thymus must transit outward across the cortex in orde r to accumulate in the SCR. Differentiation of DN cells into the CD4(+) 8() stage correlates with a reversal in polarity and migration inward, while mature cells ultimately transit the CMJ in the opposite direction of cells first entering the organ. Here we review evidence for a model in which diff erentiation is induced and proliferation is controlled by this progressive translocation of immature precursors through discrete stromal compartments. In addition, we attempt to summarize what is known about the molecular mec hanisms that may support polarized migration of early CD4(-) 8(-) thymocyte s in the adult, as well as how and where the relevant differentiative and/o r proliferative signals may be compartmentalized.